Cecropia juvenile hormones

Stereospecific Synthesis of Trisubstituted Olefins from Acetylenes or Aldehydes Applications to the Total Synthesis of Cecropia Juvenile Hormones (JH) and Farnesol... 

Epoxyfarnesol was first prepared by van Tamelen, Stomi, Hessler, and Schwartz 4 using essentially this procedure. It is based on the findings of van Tamelen and Curphey5 that N-bromosuccinimide in a polar solvent was a considerably more selective oxidant than others they tried. This method has been applied to produce terminally epoxidized mono-, sesqui-, di-, and triterpene systems for biosynthetic studies and bioorganic synthesis.6 It has also been applied successfully in a simple synthesis of tritium-labeled squalene [2,6,10,14,18,22-Tetracosahexaene, 2,6,10,15,19,23-hexamethyl-, (all-E)-] and squalene-2,3-oxide [Oxirane, 2,2-dimethyl-3-(3,7,12,16,20-pentamethyl-3,7,ll,-15,19-heneicosapentaenyl)-, (all-E)-],7 and in the synthesis of Cecropia juvenile hormone.8... 

Where would you make the first disconnection to devise a convergent synthesis for (14), whose epoxide is the cecropia juvenile hormone What reaction and what starting materials might you use ... 

Strategies based on reconnections which have been applied succesfully to sesquiterpenes, such as caryophyllene, isocaryophyllene and hirsutic acid, as well as to Cecropia juvenile hormone. 

Caryophyllenes, as an example of two naturally occurring isomeric sesquiterpenes containing a medium-sized ring, in which the success of the total syntheses lies in the stereoselective control of a chiral centre, in a common synthetic key intermediate, which governs the configuration (JE or Z) of the double bonds present in each one of the two isomers. In this context, a brief reference to Cecropia Juvenile Hormone synthesis by the Syntex group, as well as to Johnson s cationic cyclisation of unsaturated polyolefins to fused polycyclic compounds, is made. 

The Wharton-Grob fragmentation and the cationic cyclisation of polyolefins. Synthesis o/Cecropia juvenile hormone and d, -progesterone. 

It is worth noting that in this synthesis of Cecropia juvenile hormone a strategy which is the reverse of the one developed by W.S. Johnson [8] for the synthesis of steroids and other fused polycyclic systems bearing cyclohexane rings is used. This method involves a non-enzymatic cyclisation of a polyunsaturated intermediate with the appropriate stereochemistry (all-trans) (Scheme 13.3.6). Such cyclisation occurs with a really amazing stereoselectivity and several new chiral centres with the correct stereochemistry are created in one single step ... 

Draw the structure of Cecropia juvenile hormone and process it automatically. Save only the intermediate precursors which finally lead to the bicyclic compound B used by the Syntex group. 

The thiapyran ring does, like thiophene, provide a heterocyclic system on which one can perform standard sorts of reactions and then through a reductive desulfurization step expose a functionalized carbon chain. Such chemistry was first employed in a very elegant synthesis of the Cecropia juvenile hormones (Scheme 166) (73JA4444). 

Exercise 30-9 The synthesis of Cecropia juvenile hormone outlined below was designed by E. J. Corey and co-workers. Draw in the structure of the product (as i, ii, etc.) at each stage where this has been omitted, and write above the arrows the reagents and conditions necessary to accomplish reactions where these have been omitted. (To save space, the abbreviation R and R are used to designate parts of the structure that do not change in later steps.)... 

Conversion of a terminal alkyne to its alkynylsilane prevents loss of the relatively acidic terminal hydrogen (pKa of ethyne c. 25) during later synthetic steps. For example, the terminal hydrogen of propyne was masked whilst its propargylic anion was used in a synthesis of Cecropia juvenile hormone, a chemical which plays ail important role in insect development (Figure Si5.2). 

In the next examples, formaldehyde makes a primary alcohol from two deprotonated alkynes. The second reaction here (for which we have shown organolithium formation, reaction, and quench simply as a series of three consecutive reagents) forms one of the last steps of the synthesis of Cecropia juvenile hormone whose structure you met right at the beginning of the chapter. 

Diorganocuprates couple readily with vinylic halides and have been employed in the synthesis of some natural products, e.g., fulvoplumieren and Cecropia juvenile hormone (26, 27, 62, 63). Copper-halogen exchange can occur simultaneously 174, 309). Successful coupling reactions of organocopper compounds with vinylic halides are listed in Table VIII. 

Still etal have reported a highly stereoselective synthesis of the alcohol ( 4) which has been previously converted into the Cis Cecropia Juvenile Hormone (Scheme 3). The key step in this synthesis involves the recently described [2,3] sigmatropic rearrangement of the dilithio dianion derived from (13). Full details of the previously reported Ci and Cig Cecropia Juvenile Hormone syntheses have been published."... 

The same general scheme provided a synthesis of the C15 Cecropia juvenile hormone. 

It has also been used in a convenient synthesis of bishomofamesol (3), a in one synthesis of the Cis-Cecropia juvenile hormone (4)/... 

This strategy has been applied to the synthesis of the Cis Cecropia juvenile hormone (JH) (163 Scheme 13) using the ketal (160) rather than an alkoxy butadiene. Surprisingly, an a,p-unsaturated ester is obtained as an -3 1 mixture from which the undesired ( )-isomer can be separated by fractional distillation. The iterated allylic alcohol (163) is transformed into its isomeric allylic cohol which is subsequently reduced to an alkene and epoxidized to realize the target (163). The scheme also lends itself to... 

The method has been used in biogenetic-type synthesis of di- and triterpenes it has also been used in the synthesis of Cecropia juvenile hormone. ... 

Nozaki and Yamamoto reported a novel method for regiospecific isomerization of epoxides to allylic alcohols based on diethylaluminum 2,2,6,6-tetramethylpiperidide (DATMP) which can be prepared in situ from Et2AlCl and lithium 2,2,6,6-tetramethylpiperidide (LiTMP) (molar ratio 1 1) in benzene at 0 °C for 30 min [119], Reaction of DATMP (4 equiv.) with ( )-cyclododecene oxide in benzene at 0 °C for 3 h produced ( )-2-cyclododecen-l-ol in 90 % yield. Interestingly, the reaction of diepoxide 121, a useful synthetic intermediate in the preparation of Cig-Cecropia juvenile hormone, with DATMP furnished the triol 122 in 41 % yield (Sch. 83). 

R = Et) by a sequence of standard reactions. Using precisely the same methodology, Corey and Yamamoto have accomplished short and stereospecific syntheses of farnesol (25) and a positional isomer of Cecropia juvenile hormone (26) as outlined in Scheme 1. A preliminary examination of the biological activity of (26) indicates that it is very active and species specific. 

Reactions between a-thioallyllithiums and allyl halides, which usually proceed predominantly via OL-CL (head-to-head) coupling, have proved to be valuable in synthesis.They have been used successfully for example in the synthesis of 1,5-dienes such as squalene, (/ )-(-(-)-10,11-epoxyfamesol, (/ )-(+)- and (S)-(-)-2,3-oxidosqualene and mokupalide, dendrolasin, cembra-nolides, methyl ceriferate and Cecropia juvenile hormone (Scheme 25 and Scheme 26). ... 

Two original syntheses of Cis Cecropia juvenile hormones are depicted in Scheme 26, - both of which use the strategy presented above. The second synthesis is particularly ingenious since the dihydro-... 

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